Real-world eligibility for platinum doublet plus immune checkpoint inhibitors in extensive-stage small-cell lung cancer

Abstract

Introduction: Small cell lung cancer (SCLC) is a rapidly progressing aggressive malignancy. Durvalumab in CASPIAN and atezolizumab in IMPower133 were found to improve overall survival (OS) for extensive-stage SCLC. Here we evaluate the proportion of real-world ES SCLC patients who may be eligible for first-line immune checkpoint inhibitor (ICI) with platinum doublet.Methods: A retrospective cohort analysis was conducted of referred ES SCLC between 2015 and 2017 in British Columbia, Canada. Patient demographics, staging, treatment, and survival data were collected through the Cancer Registry. Retrospective chart review was completed to extract past medical history and missing variables. CASPIAN/IMPower133 excluded patients with autoimmune diseases, active infection, and performance status (PS) ≥2.Results: Between 2015 and 2017, 349 patients were diagnosed with ES SCLC. In patients who received platinum-doublet chemotherapy (n=227), 15 had medical contraindication to ICI: inflammatory bowel disease (n=4), rheumatoid arthritis (n=4), idiopathic pulmonary fibrosis (n=3), lupus (n=1), Sjogren's (n=1), Takayasu arteritis (n=1), and active tuberculosis (n=1). ECOG PS was 0-1 in 96 (45%), PS was 2 in 61 (29%), and ≥3 in 51 (10%). Prior to cycle 1, 82 (36%) patients were eligible for ICI in addition to platinum doublet, 23% of the entire ES population. After cycles 1 and 2, additional 15 (7%) and 8 (4%) patients became PS 0-1, respectively. mOS for ES SCLC who received first-line platinum doublet, non-platinum chemotherapy, and best supportive care was 8.4 1.9 and 1.5 months (p<0.001).Discussion: By CASPIAN/IMpower133 trial eligibility, only 36% of our real-world platinum-treated patients would have been eligible for the addition of ICI, which is 23% of the entire ES population in one Canadian province. After one or two cycles of chemotherapy, an additional 11% of patients showed PS improvement to 0-1. While the results of CASPIAN/IMpower133 are Frontiers in Oncology frontiersin.org 01

Brief Report: Real-World Eligibility for Clinical Trials in Patients With Extensive-Stage SCLC at a Tertiary Care Center

“…Similarly, Rittberg et al. 10 reported an additional 29% of patients with ES-SCLC in their study would have become eligible for chemoimmunotherapy if inclusion criteria were expanded to include ECOG 2.…”

Real-world impact of the introduction of chemo-immunotherapy in extended small cell lung cancer: a multicentric analysis

“…The addition of immunotherapy to first-line chemotherapy for extended SCLC has been approved for clinical practice according to randomized clinical trials ( 10 , 11 ), but its actual impact in real-world setting is thought to be impaired by clinical features of RW patients, often presenting highly symptomatic and with several comorbidities related to age and smoking habits ( 21 ). In the present study we analyzed the impact of introduction of chemo-immunotherapy in clinical practice.…”

“…In addition, clinical trials included clinically selected population, while real-world (RW) patients affected by SCLC often have relevant comorbidities, older age and high symptoms burden. In this context, the fraction of RW patients complying with pivotal clinical trials inclusion/exclusion criteria is rather limited and previously estimated as about 36% in a retrospective cohort analysis in Caucasian population ( 21 ).…”

Long-term effectiveness and treatment sequences in patients with extensive stage small cell lung cancer receiving atezolizumab plus chemotherapy: Results of the IFCT-1905 CLINATEZO real-world study.

“…Interestingly, in IFCT-1905 CLINATEZO, the majority of patients had a PS 0-1 and nearly half were < 65 years-old; in real-world cohorts, a higher proportion of patients were elderly, or had co-morbidities and poorer general condition [13][14][15]. It has been estimated that only one third of patients is actually eligible to immunotherapy [17]. Still, an unmet need remains the identification of patients actually benefiting, in terms of long-term outcomes, of this regimen; in that matter, molecular signatures have shown some promise, with a correlation between the socalled SCLC-I subtype and survival [5].…”